Gliomas are the most common and malignant of primary brain tumors in adults. Current treatments include surgical removal followed by chemotherapy. However,these procedures may themselves transform cells surrounding the lesion, leading to secondary tumors. The long-term goal of this research program seeks to identify mechanisms involved in transformation of glia. These studies will provide key insights into the development of gliomas and may identify novel targets for therapeutic intervention. The proposal focuses on the characterization of the mechanisms responsible for appropriate PDGFR expression during glial cell differentiation and examination of whether these mechanisms are defective in glial tumor cells. They physiological function of PDGFR is to control glial cell growth and differentiation during development. Overexpression of PDGFR is detected in both early and late stages of gliomas. Preliminary data suggest the PDGFR transcript does not respond to cAMP regulation in glioma cells as it does in normal glia. The hypothesis is that an altered response of PDGFR gene expression to cAMP regulation may underlie the uncontrolled proliferation of tumor cells. The specific aims of this proposal are to identify nucleotide sequences within the PDGFR gene and gene product ghat are involved in the cAMP- dependent regulatory mechanisms, and to establish a role for these factors in inducing aberrant PDGFR expression in glioma cells.